Clinical implications of irregular ADMET properties with levodopa and other antiparkinson's drugs

Introduction: Parkinson's disease is a neurodegenerative disorder characterized by the loss of striatal dopaminergic neurons. Besides the improvement of the dopaminergic loss, the treatment focuses on non-dopaminergic medication targeting motor and non-motor symptoms, and on the development of neuroprotective medication. A good knowledge of the properties of the compounds used is essential not only for those involved in pharmacological research but also for those who treat Parkinson's disease patients, facing their still many unmet needs. Areas covered: The review discusses the pharmacokinetic properties of levodopa (LD) and factors influencing them, the pharmacodynamics of LD and approaches with the aim of improving this, covering some of the other antiparkinson medications available. Among the non-dopaminergic agents, it focuses on research on kynurenines. A literature search was made in PubMed for Parkinson's disease treatment, LD, LD absorption, LD pharmacokinetics, continuous dopaminergic stimulation, LD-carbidopa intraintestinal gel therapy, dopamine agonists and monoamine oxidase-B inhibitors. Expert opinion: Various factors can cause irregularities in the pharmacokinetics of LD, with interconnected consequences on its therapeutic effect. Its long-term use is associated with the development of motor complications; this is explained mostly by pharmacodynamic and also by pharmacokinetic properties, the latter gaining importance in the advanced stages of the disease.